Remote stereocontrol in the intramolecular Diels-Alder reaction: Application to the total synthesis of (+)-dihydrocompactin

• Main Author: Johns, Deidre M
• Format: Dissertation
• Language: English
• Subjects: chemistry, organic

Methods for using remote stereocenters to induce asymmetry in the intramolecular Diels-Alder reaction were studied and used in the total synthesis of (+)-dihydrocompactin. In the synthesis of (+)-dihydrocompactin, formation of a cyclic oxocarbenium ion that incorporates the stereocenter enables it to induce asymmetry. Evidence for this intermediate was obtained by comparison to a similar substrate that is incapable of forming a cyclic oxocarbenium ion. The total synthesis includes an asymmetric crotyl-transfer reaction to enantioselectively prepare the portion of the molecule containing the key stereocenter, which influences the Diels-Alder reaction to provide the desired octalin stereochemistry. This stereocenter is subsequently used to stereoselectively form the γ-hydroxylactone by chelation with samarium in a Reformatsky-type reaction. Intramolecular Diels-Alder substrates that can form six-membered cyclic oxocarbenium ion intermediates also react diastereoselectively and the products are obtained as the hemi-ketone and enol ether cycloadducts. When formation of the cyclic oxocarbenium ion is prevented, substrates of this type react diastereoselectively via dipole-controlled transition-state structures. Evidence for dipole-control was obtained by studying the affect of Lewis acids, protecting groups and substitution on the diastereoselectivity of the reaction.